17-59210665-C-CT

Position:

• chr17-59210665-C-CT

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_018149.7(SMG8):​c.615dupT​(p.Val206fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SMG8 NM_018149.7 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -0.538

Genes affected

SMG8 (HGNC:25551): (SMG8 nonsense mediated mRNA decay factor) Involved in nuclear-transcribed mRNA catabolic process, nonsense-mediated decay and regulation of protein kinase activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000265303 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-59210665-C-CT is Pathogenic according to our data. Variant chr17-59210665-C-CT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3382841.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMG8	NM_018149.7	c.615dupT	p.Val206fs	frameshift_variant	1/4	ENST00000300917.10	NP_060619.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMG8	ENST00000300917.10	c.615dupT	p.Val206fs	frameshift_variant	1/4	1	NM_018149.7	ENSP00000300917.4
ENSG00000265303	ENST00000577660.1	c.136-4139dupT		intron_variant		3		ENSP00000464167.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Alzahrani-Kuwahara syndrome Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Juno Genomics, Hangzhou Juno Genomics, Inc

-

PM2_Supporting+PVS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-57288026;